Outcomes for Standardized Home and Hospital-Based Infusions of Infliximab for Children With Inflammatory Bowel Disease.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) is commonly treated with infliximab in a hospital setting. Utilization of home infusions (HI) is increasing due to insurance mandates, travel time savings, and convenience. We evaluated adverse outcomes (AOs) of infliximab infusions in children with IBD receiving HI compared to hospital-based infusions. METHODS: Children receiving HI between September 2016 and September 2018 were retrospectively matched based on age, race, ethnicity, sex, and disease type to a cohort receiving infliximab at a hospital-based center. A survival analysis evaluated the hazard ratio for AOs in HI relative to hospital-infused children over 2 years. AOs were defined as discontinuation of therapy for clinically relevant reasons, IBD-related hospitalizations, and emergency department visits. RESULTS: We included 102 children (51 pairs) (63% male, 91% White, 92% Crohn disease). Disease location, behavior, growth status, and disease severity were similar between the 2 cohorts. Quiescent disease increased from 3% to 93% after 2 years without cohort differences. At baseline, 94% of HI patients and 88% of controls were on 5 mg/kg every 8 weeks as standard maintenance therapy. Within 2 years, only 19% remained on 5 mg/kg and the remainder required increased dosing or decreased interval. The HI cohort had fewer labs obtained ( P < 0.001), though laboratory values, number of clinic visits, and frequency of AOs were similar. CONCLUSION: Drug durability, AOs, and laboratory values were similar between HI and hospital-based infusions. These findings suggest HI may be as effective as hospital-based infusions, provided a standardized care approach is utilized.

Online Grocery Shopping and the Supplemental Nutrition Assistance Program (SNAP) Electronic Benefit Transfer Card (EBT): Perceptions of Head Start Caregivers.

The objective of this study was to explore perceptions of online grocery shopping and the online United States Department of Agriculture's (USDA) Supplemental Nutrition Assistance Program (SNAP) Electronic Benefit Transfer card (EBT) program among Head Start caregivers. Three focus groups were conducted between December 2019 and January 2020. Most participants hadn't tried online grocery shopping. Concerns included others choosing perishables, receiving wrong items, and inappropriate substitutes. Perceived benefits included saving time, preventing impulse buys, and eating healthier. Results have broad applicability in the current COVID-19 pandemic where online grocery shopping and the online SNAP EBT program have rapidly expanded across the United States.

Surgical timing in neonatal brachial plexus palsy: A PRISMA-IPD systematic review.

BACKGROUND: Neonatal brachial plexus palsy (NBPP) is a serious complication of high-risk deliveries with controversy surrounding timing of corrective nerve surgery. This review systematically examines the existing literature and investigates correlations between age at time of upper trunk brachial plexus microsurgery and surgical outcomes. METHODS: A systematic screening of PubMed, Cochrane, Web of Science, and CINAHL databases using PRISMA-IPD guidelines was conducted in January 2020 to include full-text English papers with microsurgery in upper trunk palsy, pediatric patients. Spearman rank correlation analysis and two-tailed t-tests were performed using individual patient data to determine the relationship between mean age at time of surgery and outcome as determined by the Mallet, Medical Research Council (MRC), or Active Movement Scale (AMS) subscores. RESULTS: Two thousand nine hundred thirty six papers were screened to finalize 25 papers containing individual patient data (n = 256) with low to moderate risk of bias, as assessed by the ROBINS-I assessment tool. Mallet subscore for hand-to-mouth and shoulder abduction, AMS subscore for elbow flexion and external rotation, and MRC subscore for elbow flexion were analyzed alongside the respective age of patients at surgery. Spearman rank correlation analysis revealed a significant negative correlation (ρ = -0.30, p < .01, n = 89) between increasing age (5.50 ± 2.09 months) and Mallet subscore for hand-to-mouth (3.43 ± 0.83). T-tests revealed a significant decrease in Mallet hand-to-mouth subscores after 6 months (p < .05) and 9 months (p < .05) of age. No significant effects were observed for Mallet shoulder abduction, MRC elbow flexion, or AMS elbow flexion and external rotation. CONCLUSION: The cumulative evidence suggests a significant negative correlation between age at microsurgery and Mallet subscores for hand-to-mouth. However, a similar correlation with age at surgery was not observed for Mallet shoulder abduction, MRC elbow flexion, AMS external rotation, and AMS elbow flexion subscores.

Silver Nanoparticles and Its Mechanistic Insight for Chronic Wound Healing: Review on Recent Progress.

Wounds are structural and functional disruptions of skin that occur because of trauma, surgery, acute illness, or chronic disease conditions. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase, and finally the tissue remodeling. Therefore, these processes are extensively studied to develop novel therapeutics in order to achieve maximum recovery with minimum scarring. Several growth hormones and cytokines secreted at the site of lesions tightly regulates the healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold and zinc) are increasingly being employed in dermatology due to their favorable effects on healing, as well as in treating and preventing secondary bacterial infections. In the current review, a brief introduction on traditional would healing approach is provided, followed by focus on the potential of wound dressing therapeutic techniques functionalized with Ag-NPs.

Direct Sciatic Nerve Electrical Stimulation for Complex Regional Pain Syndrome Type 1.

OBJECTIVE: Foot and leg pain in complex regional pain syndrome (CRPS) presents a challenge even with neuromodulation techniques such as spinal cord stimulation (SCS). We report our experience with a novo technique of direct sciatic nerve electrical stimulation (DISNES) for intractable foot and leg pain in CRPS I. MATERIALS AND METHODS: Following Research Ethics Board (REB) approval, data were gathered for 16 patients (10 women and 6 men, age 26-61 years) who had been subjected to ipsilateral DISNES. All 16 patients had failed conventional medical management. As well, seven subjects were previously treated with SCS for CRPS I pain. These subjects reported pain relief in the thigh and leg, however the SCS was unable to alleviate the disabling foot pain despite varied and multiple programming techniques. The remaining nine subjects were treated primarily with DISNES. Evaluation was done using visual analog scale (VAS), Oswestry Disability Index version 2 (ODI), and quality of life (EQ-5D and SF-36) scores done both pre-DISNES and at two follow-ups. RESULTS: VAS scores decreased by 59% at follow-up (F/U) 1 (P = 0.00001) and 46% F/U 2. ODI improving by 40% F/U 1 (P = 0.0038) and 37% F/U 2. SF-36 scores improved by 69% F/U 1 (P = 0.015) and 80% F/U 2. EQ-5D scores improved significantly by F/U 1 (P = 0.00030) but insignificantly at F/U 2 (P = 0.81). There was also a rapid resolution of autonomic features such as edema, hyperemia, and allodynia (within 7-10 days). Three subjects returned to work post-DISNES. CONCLUSION: Our study shows that DISNES helps to control the disabling foot pain in CRPS I, thus improving the quality of life, improving ambulation and decreasing disability. DISNES also alleviates autonomic features and dystonia in CRPS I. Further studies are needed to determine long-term efficacy as this study pool is limited in size and follow-up period.

Destabilization potential of phenolics on Aß fibrils: mechanistic insights from molecular dynamics simulation.

The clinical signature of Alzheimer's disease (AD) is the deposition of aggregated Aß fibrils that are neurotoxic to the brain. It is the major form of dementia affecting older people worldwide, impeding their normal function. Finding and testing various natural compounds to target and disrupt stable Aß fibrils seems to be a promising and attractive therapeutic approach. Four phenolic compounds from plant sources were taken into consideration for the present work, and were initially screened by docking. Ellagic acid (REF) came out to be the best binder of the Aß oligomer from docking studies. To test the destabilization effect of REF on the Aß oligomer, MD simulation was conducted. The simulation outcome obtained clearly indicates a drift of terminal chains from the Aß oligomer, leading to the disorganization of the characteristically organized cross ß structure of the Aß fibrils. Increased values of RMSD, Rg, RMSF, and SASA are indicative of the destabilization of the Aß fibril in the presence of REF. The disruption of salt bridges and a notable decline in the number of hydrogen bonds and ß-sheet content explain the conformational changes in the Aß fibril structure, ceasing their neurotoxicity. The MM-PBSA results revealed the binding of REF to chain A of the Aß oligomer. The destabilization potential of ellagic acid, as explained by the MD simulation study, establishes it as a promising drug for curing AD. The molecular-level details about the destabilization mechanism of ellagic acid encourage the intensive mining of other natural compounds for therapeutic intervention for AD.

Isotretinoin and α-tocopherol acetate-loaded solid lipid nanoparticle topical gel for the treatment of acne.

AIMS: This study was aimed to develop Isotretinoin (ITN) and α-tocopherol acetate (α-TA) loaded solid lipid nanoparticle topical gel for better skin sensitivity and potentiation of efficacy. METHODS: ITN and α-TA-loaded solid lipid nanoparticles (AE-SLN) were prepared by microemulsion method with glyceryl mono-stearate as lipid and tween 80: butanol as surfactantmix and characterised. AE-SLN gel was evaluated for physicochemical characteristics, drug release, skin irritation and anti-acne activity in rats. RESULTS: AE-SLNs had mean particle size of 193.4 nm (zeta-potential -29 mV) and entrapment efficiency of 84%w/w for ITN and 77.4%w/w for α-TA. AE-SLN gel showed sustained drug release for 24 h with a final cumulative release of 95.8% w/w and 89.1%w/w for ITN and α-TA. AE-SLN gel showed no erythema or edoema in rabbits and potent efficacy in rat model of acne. CONCLUSION: In conclusion, AE-SLN gel has the potential to use as a non-irritant topical formulation for the treatment of acne.

Abdominal migraines: Variations in diagnosis and care between pediatric gastroenterologists and neurologists. / Migraña Abdominal: Variaciones en el diagnóstico y tratamiento entre gastroenterólogos y neurólogos pediatras.

INTRODUCTION: Abdominal migraine (AM) is uncommon and understudied. Our objective was to investigate the diagnosis and treatment of children and adolescents with AM and compare with that of pediatric gastroenterologists and neurologists. PATIENTS AND METHOD: All AM cases (1-18 years) from a USA hospital with diagnosis of abdominal migraine or its variants (ICD-9 346.2 or IC-10 G43.D, G43.D0, G43.D1) between 2011 and 2017 were reviewed. Information on diagnosis, interval from onset of symptoms, diagnostic criteria, diagnostic tests, treatment, and outcome were analyzed. RESULTS: 69 medical records were identified. The mean age at diagnosis was 9.7 years, and 48% of patients were female. 50/69 (72.4%) patients were exclusively treated by a pediatric gastroenterologist and 10/69 (14.5%) exclusively by a pediatric neurologist. 6/69 (8.7%) were initially evaluated by gas troenterology and referred to neurology, and 2/69 (2.9%) were initially evaluated by neurology and then referred to gastroenterology. 3/10 (30%) of the AM diagnosed by neurologists did no report ab dominal pain (AP), however, all diagnoses made by gastroenterologists did (p = 0.0035). 5/50 (10%) of the gastroenterology medical records and no neurology medical records mentioned Rome criteria. CONCLUSIONS: Most of the children were diagnosed by pediatric gastroenterologists. Gastroenterolo gists rarely use the Rome criteria. Patients evaluated by neurologists are frequently diagnosed with AM even without AP (a criterion that is required for its diagnosis). Education is recommended for the correct and timely diagnosis of AM.

A Quality Improvement Approach to External Infliximab Infusions in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: We used a quality improvement (QI) approach to improve access and reduce barriers to care by increasing the number of external infliximab infusions at our pediatric inflammatory bowel disease center. METHODS: Using an iterative QI strategy, pediatric patients ≥12 years of age with inflammatory bowel disease were offered the opportunity to receive infliximab infusions at home/an external infusion center. They were required to first have >5 infusions at the hospital without any significant infusion reactions. Data were collected and tracked monthly using P-charts. Comparisons between control chart centerlines were analyzed using the Fisher exact test. RESULTS: Fifty-four patients received external infusions, 87% had Crohn disease, 63% boys, average age 17.6 ±â€Š2.9 years, and 89% with private insurance. From September 2016 to January 2018, the percentage of eligible patients receiving external infusions was approximately 7%, increasing to approximately 30% by January 2018. A centerline shift, representing a statistically significant change, occurred in October 2016 and June 2017 (P < 0.001). No serious safety concerns have occurred. CONCLUSIONS: Through a multidisciplinary team of stakeholders using QI strategies, we now offer external infusion service options to all appropriate patients as routine practice. Home infusions are a viable option to reduce barriers to care, and our patients did not experience any safety events.

Caffeine destabilizes preformed Aß protofilaments: insights from all atom molecular dynamics simulations.

The aggregation and deposition of neurotoxic Aß fibrils are key in the etiology of Alzheimer's disease (AD). It has been clinically recognized as a major form of dementia across the globe. Finding and testing various natural compounds to target Aß fibrils to disrupt their stable structures seems to be a promising and attractive therapeutic strategy. The destabilization effects of caffeine on Aß fibrils are investigated via in silico studies, where a series of molecular dynamics (MD) simulations, each of 100 ns, was conducted. The simulation outcomes obtained henceforth clearly indicated the drift of the terminal chains from the protofibrils, leading to disorganization of the characteristically organized cross-ß structures of Aß fibrils. The structural instability of Aß17-42 protofibrils is explained through enhanced fluctuations in the RMSD, radius of gyration and RMSF values in the presence of caffeine. The key interactions providing stability, comprising D23-K28 salt bridges, intra- and inter-chain hydrogen bonding and hydrophobic interactions involving interchain A21-V36 and F19-G38 and intrachain L34-V36, were found to be disrupted due to increases in the distances between the participating components. The loss of ß-sheet structure with the introduction of turns and α-helices in terminal chains may further inhibit the formation of higher order aggregates, which is necessary to stop the progression of the disease. The atomistic details obtained via MD studies relating to the mechanism behind the underlying destabilization of Aß17-42 protofibrils by caffeine encourage further investigations exploring the potency of natural compounds to treat AD via disrupting preformed neurotoxic Aß protofibrils.

Higher Growth Rate of Branch Duct Intraductal Papillary Mucinous Neoplasms Associates With Worrisome Features.

BACKGROUND & AIMS: For patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs, cysts), it is a challenge to identify those at high risk for malignant lesions. We sought to identify factors associated with development of pancreatic cancer, focusing on neoplasm growth rate. METHODS: We performed a retrospective study of 189 patients with BD-IPMNs who underwent at least 2 contrast-enhanced cross-sectional imaging studies, 1 year or more apart, at a tertiary referral center from January 2003 through 2013. Patients with cysts that had Fukuoka worrisome or high-risk features were excluded. Two radiologists reviewed all images. Cyst size was recorded at the initial and final imaging studies and growth rate was calculated. We collected patient demographic data, cyst characteristics, and clinical outcomes; univariate logistic regression models were used to determine the odds of developing worrisome features. The primary outcomes were to determine growth rate of low-risk BD-IPMNs and to assess whether cyst growth rate correlates high-risk features of IPMNs. RESULTS: Based on image analyses, cysts were initially a median 11 mm (range, 3-31 mm) and their final size was 12.5 mm (range, 3-42 mm). After a median follow-up time of 56 months (range, 12-163 months), the median cyst growth rate was 0.29 mm/year. Twelve patients developed worrisome features, no patients developed high-risk features, 4 patients had surgical resection, and no cancers developed. The rate of BD-IPMN growth was greater in patients who developed worrisome features than those who did not (2.84 mm/year vs 0.23 mm/year; P < .001). The odds of developing worrisome features increased for each unit (mm) increase in cyst size (odds ratio, 1.149; 95% CI, 1.035-1.276, P = .009). CONCLUSION: In a retrospective analysis of images from patients with BD-IPMN, we found low-risk BD-IPMNs to grow at an extremely low rate (less than 0.3 mm/year). BD-IPMNs in only about 6% of patients developed worrisome features, and none developed high-risk features or invasive cancers. BD-IPMNs that developed worrisome features were associated with a significantly higher rate of growth than lesions with low-risk features. Low risk BD-IPMNs that grow more than 2.5 mm/year might require surveillance.

Comparison of the peripheral antinociceptive effect of somatostatin with bupivacaine and morphine in the rodent postoperative pain model.

BACKGROUND AND OBJECTIVES: Infiltration of surgical wound with local anaesthetics attenuate postoperative pain. However, side effects can also occur. Somatostatin (SST) and its analogues like octreotide reportedly reduce peripheral sensitisation. The current study evaluates peripherally mediated antinociceptive effect of SST in a rat model of postoperative pain. This was compared with bupivacaine and morphine under identical experimental conditions. DESIGN: Randomised vehicle-controlled blind study. SETTING: Pain research laboratory, All India Institute of Medical Sciences, New Delhi from February 2014 to July 2017. EXPERIMENTAL SUBJECT: Rodent hind paw incision model. INTERVENTIONS: Sprague-Dawley rats were subjected to incision and one of the following drugs administered into the open wound once by a micropipette: SST (10, 30 or 100 µg), bupivacaine (3, 10, 30, 50 or 100 µg) or morphine (100 µg). Antinociceptive effect of SST was further evaluated for its reversibility, site of action, effect on spinal c-fos expression and blood glucose level. The site of action of morphine was also investigated. MAIN OUTCOME MEASURE: Nociception was estimated by nonevoked (guarding behaviour) and evoked (mechanical allodynia and thermal hyperalgesia) pain behaviours between 2 h and days 4 to 7. RESULTS: Nociception was maximum 2 h after incision. SST (10 to 100 µg) significantly attenuated guarding behaviour between 2 h and day 2. A delayed inhibitory effect was observed on allodynia. Bupivacaine (10 to 100 µg doses) similarly decreased guarding score up to day 2 though evoked pain behaviours were relatively unaffected. In contrast, morphine produced a potent but transient inhibitory effect on guarding score at 2 h, which was mediated by both peripheral and central opioid receptors. The antinociceptive effect of SST was peripherally mediated by type 2 receptors and was associated with decreased c-fos staining. Blood glucose level was unaltered. CONCLUSION: Guarding behaviour, which likely represents pain-at-rest following surgery, was attenuated by both bupivacaine and SST to comparable extents. This novel peripherally mediated antinociceptive effect of SST needs further evaluation.

Hospital cultural competency as a systematic organizational intervention: Key findings from the national center for healthcare leadership diversity demonstration project.

BACKGROUND: Cultural competency or the ongoing capacity of health care systems to provide for high-quality care to diverse patient populations (National Quality Forum, 2008) has been proposed as an organizational strategy to address disparities in quality of care, patient experience, and workforce representation. But far too many health care organizations still do not treat cultural competency as a business imperative and driver of strategy. PURPOSES: The aim of the study was to examine the impact of a systematic, multifaceted, and organizational level cultural competency initiative on hospital performance metrics at the organizational and individual levels. METHODOLOGY/APPROACH: This demonstration project employs a pre-post control group design. Two hospital systems participated in the study. Within each system, two hospitals were selected to serve as the intervention and control hospitals. Executive leadership (C-suite) and all staff at one general medical/surgical nursing unit at the intervention hospitals experienced a systematic, planned cultural competency intervention. Assessments and interventions focused on three organizational level competencies of cultural competency (diversity leadership, strategic human resource management, and patient cultural competency) and three individual level competencies (diversity attitudes, implicit bias, and racial/ethnic identity status). In addition, we evaluated the impact of the intervention on diversity climate and workforce diversity. FINDINGS: Overall performance improvement was greater in each of the two intervention hospitals than in the control hospital within the same health care system. Both intervention hospitals experienced improvements in the organizational level competencies of diversity leadership and strategic human resource management. Similarly, improvements were observed in the individual level competencies for diversity attitudes and implicit bias for Blacks among the intervention hospitals. Furthermore, intervention hospitals outperformed their respective control hospitals with respect to diversity climate. PRACTICE IMPLICATIONS: A focused and systematic approach to organizational change when coupled with interventions that encourage individual growth and development may be an effective approach to building culturally competent health care organizations.

Palliation of Brain Metastases: Analysis of Prognostic Factors Affecting Overall Survival.

CONTEXT: Brain metastasis is one of the most feared complications of cancer that poses significant mortality and morbidity in patients with advanced cancer. The incidence is rising because of greater use of magnetic resonance imaging and spectroscopy; and increased survival from recent advances in immunotherapy and modern radiotherapy techniques. Despite all, the prognosis remains poor. AIMS: This study aimed to analyze prognostic factors and overall survival in patients with brain metastases. SUBJECTS AND METHODS: A total of 145 patients were analyzed from July 2014 to June 2015 for various prognostic factors prospectively. Survival analysis was done using Kaplan-Meier curve. RESULTS: The median overall survival was 6 months, while 1- and 2-year survival rates were 8.3% and 1.4%, respectively. Median survival was highest with surgery followed by radiotherapy (11 months). Whole-brain radiotherapy (WBRT) significantly improved the survival (P = 0.006). The most common primary was lung cancer (58%) and the most common histology was adenocarcinoma (36%). Most patients (38%) were diagnosed upfront with brain metastases. Most of the lesions were multiple (80%) and located in cerebrum (58%). Survival was significantly improved with female gender (P = 0.003), Eastern Cooperative Oncology Group performance status (PS) 0-2 (P = 0.006), breast primary (P = 0.004), time lag of >6 months (P < 0.001), solitary lesion (P = 0.002), and controlled primary (P = 0.017). CONCLUSIONS: WBRT remains the cornerstone of the management of brain metastases. The present study concludes that the survival of patients with brain metastases is significantly improved with female gender, good PS, primary breast cancer, time lag of >6 months between diagnosis of the primary tumor and development of brain metastases, solitary lesion, and controlled primary tumor.

Inhibition and Reversal of Microbial Attachment by an Antibody with Parasteric Activity against the FimH Adhesin of Uropathogenic E. coli.

Attachment proteins from the surface of eukaryotic cells, bacteria and viruses are critical receptors in cell adhesion or signaling and are primary targets for the development of vaccines and therapeutic antibodies. It is proposed that the ligand-binding pocket in receptor proteins can shift between inactive and active conformations with weak and strong ligand-binding capability, respectively. Here, using monoclonal antibodies against a vaccine target protein - fimbrial adhesin FimH of uropathogenic Escherichia coli, we demonstrate that unusually strong receptor inhibition can be achieved by antibody that binds within the binding pocket and displaces the ligand in a non-competitive way. The non-competitive antibody binds to a loop that interacts with the ligand in the active conformation of the pocket but is shifted away from ligand in the inactive conformation. We refer to this as a parasteric inhibition, where the inhibitor binds adjacent to the ligand in the binding pocket. We showed that the receptor-blocking mechanism of parasteric antibody differs from that of orthosteric inhibition, where the inhibitor replaces the ligand or allosteric inhibition where the inhibitor binds at a site distant from the ligand, and is very potent in blocking bacterial adhesion, dissolving surface-adherent biofilms and protecting mice from urinary bladder infection.

Customized Minimally Invasive Orbital Decompression Surgery Improves Lower Eyelid Retraction and Contour in Thyroid Eye Disease.

PURPOSE: To investigate the outcome of a customized approach with targeted zygomatic basin bone removal orbital decompression in lower eyelid retraction and contour of patients with thyroid eye disease. METHODS: In a comparative case series, clinical charts and photos of a consecutive sample of 92 patients with thyroid eye disease submitted to different types orbital decompression were studied. Exophthalmos, midpupil to lower eyelid margin distances (MRD2) at 11 meridians, and globe position were measured and compared according to the types of decompression. Each eyelid was also labeled as within or outside normal limits regarding both contour pattern analysis and MRD2 compared with a control normal range. Eyelid contour and globe position from patients with orbital decompression with zygomatic basin removal were compared with those without basin removal. RESULTS: A total of 105 orbits from 57 patients met the study inclusion criteria. Ninety-eight orbits had lateral orbital wall decompression and in 53% of these cases, bone in the zygomatic basin was removed. Removal of the zygomatic basin did not significantly enhance decrease in proptosis, but significantly induced vertical globe descent and improved MRD2 (p < 0.05). Preoperatively, 37% of the eyelids were in the normal MRD2 range and 18% within the normal contour range. Preoperatively, 77% had normal MRD2 and 55% normal contour range. CONCLUSIONS: Our study findings support the practical utility of incorporating a customized approach to orbital decompression, and suggest that an individualized approach with targeted bone removal may obviate the need for additional surgeries such as lower eyelid retraction repair.

Succession Planning and Financial Performance: Does Competition Matter?

Succession planning has been defined as the process by which one or more successors are identified for key positions, development activities are planned for identified successors, or both. Limited research exists pertaining to the relationship between hospital succession planning and financial performance, particularly in the context of market competition. We used the resource-based view framework to analyze the differential effect of succession planning on hospitals' financial performance based on market competition. According to RBV, organizations can achieve higher performance by using their superior resources and capabilities. We used a panel design consisting of a national sample of hospitals in the United States for 2006-2010. We analyzed data using multivariate linear regression with facility random effects and year and state fixed effects. The sample included 22,717 hospital-year observations; more than one half of the hospitals (55.4%) had a succession planning program. The study found a positive relationship between the presence of succession planning and financial performance (ß = 1.41, p < .01), which was stronger in competitive markets (ß = 2.31, p = .03) than in monopolistic markets (ß = 1.06, p = .01). Hospitals can use these results to make informed decisions about investing in succession planning programs on the basis of competition in their market.

Compressive Optic Neuropathy and Repeat Orbital Decompression: A Case Series.

PURPOSE: To characterize the presenting characteristics, preoperative clinical activity score (CAS), surgical approach, and visual outcomes in patients with thyroid eye disease undergoing repeat orbital decompression for recurrent or recalcitrant compressive optic neuropathy (CON). METHODS: The medical records of patients with recurrent or recalcitrant CON undergoing repeat orbital decompressions were retrospectively reviewed. The primary outcome measures included pre- and postoperative Humphrey visual field mean deviation, visual acuity (VA) measured in logarithm of the minimal angle of resolution, color vision measured by Ishihara plates, and presence of relative afferent pupillary defect. Details of the surgical procedure and each patient's CAS at presentation were also recorded. RESULTS: Six patients, 9 orbits, with a mean preoperative CAS of 3.8 were included in this review. The mean time between initial decompression and presentation to our center for recurrent or persistent CON symptoms was 8.6 years (range, 1 to 15 years). At presentation, the average Humphrey visual field mean deviation was -16.5 (standard deviation: 8.8), improving to -3.8 (2.4) postoperatively with a mean of 9.3 months follow up (mean improvement of 75%). Preoperative VA was 0.34 (0.23) LogMAR, improving to 0.05 (0.10) LogMAR with a mean follow up of 10.4 months. Pre- to postoperative comparisons of clinical measures all showed statistically significant improvement (p < 0.05). Eight eyes presented with decreased VA (any VA < 20/20), 4 with decreased color vision (any color vision < 11), and 1 with a relative afferent pupillary defect, and all these patients demonstrated improvement following repeat orbital decompression. CONCLUSIONS: In patients with thyroid eye disease, symptoms of recurrent CON occurred up to 15 years following initial orbital decompression underscoring the smoldering, progressive nature of the disease. Repeat decompression that focused on the orbital apex resulted in visual improvement in all 6 patients. Despite clinical evidence of CON, the mean CAS of these patients at presentation was only 3.8, highlighting the importance of close monitoring of patients with thyroid eye disease following decompression regardless of the external manifestations of disease activity.

Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain.

Nucleosome positioning maps of several organisms have shown that Transcription Start Sites (TSSs) are marked by nucleosome depleted regions flanked by strongly positioned nucleosomes. Using genome-wide nucleosome maps and histone variant occupancy in the mouse liver, we show that the majority of genes were associated with a single prominent H2A.Z containing nucleosome in their promoter region. We classified genes into clusters depending on the proximity of H2A.Z to the TSS. The genes with no detectable H2A.Z showed lowest expression level, whereas H2A.Z was positioned closer to the TSS of genes with higher expression levels. We confirmed this relation between the proximity of H2A.Z and expression level in the brain. The proximity of histone variant H2A.Z, but not H3.3 to the TSS, over seven consecutive nucleosomes, was correlated with expression. Further, a nucleosome was positioned over the TSS of silenced genes while it was displaced to expose the TSS in highly expressed genes. Our results suggest that gene expression levels in vivo are determined by accessibility of the TSS and proximity of H2A.Z.